Safety and immunogenicity of DNA vaccines encoding Ebolavirus and Marburgvirus wild-type glycoproteins in a phase I clinical trial.
2015 Feb 15
Journal Article
Authors:
Sarwar, U.N.;
Costner, P.;
Enama, M.E.;
Berkowitz, N.;
Hu, Z.;
Hendel, C.S.;
Sitar, S.;
Plummer, S.;
Mulangu, S.;
Bailer, R.T.;
Koup, R.A.;
Mascola, J.R.;
Nabel, G.J.;
Sullivan, N.J.;
Graham, B.S.;
Ledgerwood, J.E.
Secondary:
J Infect Dis
Volume:
211
Pagination:
549-57
Issue:
4
PMID:
25225676
Keywords:
Adult; Antibodies, Viral; Cytokines; Ebola Vaccines; Ebolavirus; Enzyme-Linked Immunospot Assay; Female; Humans; Male; Marburgvirus; Middle Aged; T-Lymphocytes; Vaccines, DNA; Viral Vaccines; Young Adult
Abstract:
BACKGROUND: Ebolavirus and Marburgvirus cause severe hemorrhagic fever with high mortality and are potential bioterrorism agents. There are no available vaccines or therapeutic agents. Previous clinical trials evaluated transmembrane-deleted and point-mutation Ebolavirus glycoproteins (GPs) in candidate vaccines. Constructs evaluated in this trial encode wild-type (WT) GP from Ebolavirus Zaire and Sudan species and the Marburgvirus Angola strain expressed in a DNA vaccine.METHODS: The VRC 206 study evaluated the safety and immunogenicity of these DNA vaccines (4 mg administered intramuscularly by Biojector) at weeks 0, 4, and 8, with a homologous boost at or after week 32. Safety evaluations included solicited reactogenicity and coagulation parameters. Primary immune assessment was done by means of GP-specific enzyme-linked immunosorbent assay.RESULTS: The vaccines were well tolerated, with no serious adverse events; 80% of subjects had positive enzyme-linked immunosorbent assay results (≥30) at week 12. The fourth DNA vaccination boosted the immune responses.CONCLUSIONS: The investigational Ebolavirus and Marburgvirus WT GP DNA vaccines were safe, well tolerated, and immunogenic in this phase I study. These results will further inform filovirus vaccine research toward a goal of inducing protective immunity by using WT GP antigens in candidate vaccine regimens.CLINICAL TRIALS REGISTRATION: NCT00605514.
